Is CUL2 p.Ala671Val (c.2012C>T) pathogenic?

CUL2 p.Ala671Val (c.2012C>T) is classified Uncertain significance in CUL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: ambiguous (0.359); Absent from gnomAD v4.1.

How common is CUL2 p.Ala671Val (c.2012C>T) in the general population?

CUL2 p.Ala671Val (c.2012C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUL2 p.Ala671Val (c.2012C>T)?

AlphaMissense predicts ambiguous (score 0.359) — an in-silico prediction, not a clinical call.

CUL2 p.Ala671Val

c.2012C>T · VCV4657676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.359 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.359	ambiguous
REVEL	0.33	indeterminate
SaProt	LLR -7.20	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 6,019 bp · p 0.0021 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CUL2
Protein: p.Ala671Val
Coding: c.2012C>T
MANE Select: NM_003591
Type: single nucleotide variant
Location: chr10:35011942 (GRCh38)
Gene constraint: LOEUF 0.305 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.02 · 42 PDB
Residue 671: an α-helix

Full CUL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CUL2 p.Ala671Ser Uncertain significance ★ ⚠ same residue
CUL2 p.Arg148= Benign ★★ same type
CUL2 c.1110+1G>A Uncertain significance ★ same type
CUL2 c.-22-2881A>G Uncertain significance ★ same type
CUL2 c.-2C>A Uncertain significance ★ same type
CUL2 p.Ala403Val Uncertain significance ★ ⚠ same type
CUL2 p.Ala522Val Uncertain significance ★ ⚠ same type
CUL2 p.Ala634Ser Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cul2-p-ala671val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown